Is OPA1 p.Leu55fs (c.164dup) pathogenic?

OPA1 p.Leu55fs (c.164dup) is classified Likely pathogenic in OPA1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2021-01-19). No gnomAD frequency available for this variant; Associated with autosomal dominant optic atrophy, classic form.

What condition is associated with OPA1 p.Leu55fs (c.164dup)?

OPA1 p.Leu55fs (c.164dup) is associated with autosomal dominant optic atrophy, classic form (ClinVar).

How common is OPA1 p.Leu55fs (c.164dup) in the general population?

OPA1 p.Leu55fs (c.164dup) is no gnomAD frequency available for this variant (gnomAD).

How is Autosomal dominant optic atrophy, classic form inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

OPA1 p.Leu55fs

c.164dup · rs1728771454 · VCV997031

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

autosomal dominant optic atrophy, classic form

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 2 of 31
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.22	GERP -3.1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: OPA1
Protein: p.Leu55fs
Coding: c.164dup
MANE Select: NM_130837
dbSNP: rs1728771454
Type: Duplication
Location: chr3:193614852 (GRCh38)
Gene constraint: LOEUF 0.503 · pLI 0.92 (gnomAD)
Structure: AlphaFold pLDDT 74.02 · 11 PDB

Full OPA1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

autosomal dominant optic atrophy, classic form — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Autosomal dominant optic atrophy, classic form (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Adult, Childhood
Prevalence: 1-9 / 100 000 (Worldwide)

Similar variants

OPA1 p.Gly464fs Pathogenic/Likely pathogenic ★★ same condition
OPA1 p.Asn906fs Pathogenic ★ same condition
OPA1 p.Ile24fs Pathogenic ★ same condition
OPA1 p.Ile437fs Likely pathogenic ★ same condition
OPA1 p.Tyr917Ter Pathogenic same condition
OPA1 c.1035+5G>A Pathogenic/Likely pathogenic ★★ same condition
OPA1 c.1149+1G>T Likely pathogenic ★★ same condition
OPA1 c.1230+5G>A Pathogenic/Likely pathogenic ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/opa1-p-leu55fs (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown